Cyclic, or rhythmic, events are ubiquitous in nature. In recent years it has become evident that one class of biological rhythms with a periodicity approximating a day, circadian rhythms, represent a major factor in the organization of an animal's internal milieu to provide maximal adaptation with its environment. The purpose of this research program is to identify and analyze the central neural mechanisms which are responsible for the production of circadian rhythms in mammals. Previous work has been dedicated to problems of localization of function. This work has identified the retinohypothalamic projection to the suprachiasmatic nucleus of the hypothalamus and shown it mediates entrainment of circadian rhythms. Ablation of the suprachiasmatic nucleus appears to abolish circadian rhythms suggesting that the nucleus is an important component of central circadian oscillating mechanisms. The proposed work will further analyze this by studying the effects of a variety of lesions on entrainment and maintenance of circadian rhythms. These will be performed in developing and adult animals. Further studies will examine the ontogeny of circadian rhythmicity in the nucleus, the morphological development of the nucleus in vivo and in vitro, and the detailed organization of the nucleus and its afferent and efferent projections. The goal is to determine if the suprachiasmatic nucleus is a central circadian oscillating system in the mammalian brain and to characterize, as completely as possible, the organization and properties of such a system which serves a unique and important function in the mammalian nervous system.